The therapeutic use of an agent to block inappropriate or excessive secretion of endogenous adrenocortical sodium-retaining, potassium-excreting (mineralocorticoid) hormones in various disorders in man is well established. One such mineralocorticoid antagonist and potassium-sparing diuretic, spironolactone U.S.P., has been in clinical use for more than 25 years. Despite its efficacy, the administration of spironolactone leads to the undesirable side effects of gynecomastia and impotence in men and menstrual irregularities in women. In addition, its tumorogenicity in long-term studies in rodents has led the Food and Drug Administration (F.D.A. Drug Bulletin, p. 33, August-October 1976) to recommend restriction of the use of spironolactone to patients in whom other therapy is inadequate. Such side effects are considered to be the result of interaction of the drug with gonadal steroid hormone biosynthetic and target cell receptor systems (the occurrence of such side effects can be predicted by measuring their cross-reactivity toward mammalian androgen target cell receptors).
Dodson and Tweit, in U.S. Pat. No. 2,904,560, described a group of 7.alpha.-acylthio-4-pregnene-3,20-diones which were said to possess both hormonal and anti-hormonal activities consisting of cortisone-like (anti-inflammatory) and progestational hormonal activity, and inhibition of the sodium-retaining effects of desoxycorticosterone. The patent does not disclose which acylthio derivatives are glucocorticoid or progestational hormones and which are mineralocorticoid anti-hormones (it is recognized that all of these activities are unlikely to reside in a single compound).
Two 7.alpha.-acetylthio-4-pregnenediones found useful in the practice of the present invention, namely 7.alpha.-acetylthio-4-pregnene-3,20-dione and 7.alpha.-acetylthio-21-acetoxy-4-pregnene-3,20-dione, have previously been described by R. E. Schaub and M. J. Weiss, J. Org. Chem. 26:3915, 1961, but without any disclosure of possible therapeutic applications.